rs751756118

Variant names:

• chr10-63208361-T-C
• rs751756118
• NM_032776.3:c.3308A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_032776.3(JMJD1C):​c.3308A>G​(p.Asn1103Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01
• Publications: 4 publications found

Genes affected

JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

JMJD1C Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2926706).
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.3308A>G	p.Asn1103Ser	missense	Exon 10 of 26	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.3194A>G	p.Asn1065Ser	missense	Exon 9 of 25	NP_001309181.1
	JMJD1C	NM_001282948.2		c.2762A>G	p.Asn921Ser	missense	Exon 9 of 25	NP_001269877.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.3308A>G	p.Asn1103Ser	missense	Exon 10 of 26	ENSP00000382204.2	Q15652-1
	JMJD1C	ENST00000542921.5	TSL:1	c.2762A>G	p.Asn921Ser	missense	Exon 9 of 25	ENSP00000444682.1	Q15652-3
	JMJD1C	ENST00000402544.5	TSL:1	n.3280A>G		non_coding_transcript_exon	Exon 7 of 22

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249196 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000513 AC: 75 AN: 1461712 Hom.: 0 Cov.: 33 AF XY: 0.0000536 AC XY: 39 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111854

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Early myoclonic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.089	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.11		Gain of glycosylation at N1103 (P = 0.013)
MVP		0.87
MPC		0.37
ClinPred		0.27	T
GERP RS		5.6
Varity_R		0.47
gMVP		0.53
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751756118; hg19: chr10-64968121;